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Spencer T. Adams

Bio: Spencer T. Adams is an academic researcher from University of Massachusetts Medical School. The author has contributed to research in topics: Luciferin & Luciferase. The author has an hindex of 8, co-authored 9 publications receiving 392 citations.

Papers
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Journal ArticleDOI
TL;DR: Injection of mice with a synthetic luciferin, CycLuc1, improves BLI with existing luciferase reporters and enables imaging in the brain that could not be achieved with D-luciferin.
Abstract: Firefly luciferase is the most widely used optical reporter for noninvasive bioluminescence imaging (BLI) in rodents. BLI relies on the ability of the injected luciferase substrate D-luciferin to access luciferase-expressing cells and tissues within the animal. Here we show that injection of mice with a synthetic luciferin, CycLuc1, improves BLI with existing luciferase reporters and enables imaging in the brain that could not be achieved with D-luciferin.

143 citations

Journal ArticleDOI
TL;DR: Recent work to replace the natural luciferase substrate with synthetic analogs that extend the scope of bioluminescence imaging is described.

112 citations

Journal ArticleDOI
TL;DR: Firefly luciferase substrate d-luciferin and its analogs are fatty acid mimics that are ideally suited to probe the chemistry of enzymes that release fatty acid products and serve as exemplary reagents for greatly improved bioluminescence imaging in FAAH-expressing tissues such as the brain.
Abstract: Firefly luciferase is homologous to fatty acyl-CoA synthetases. We hypothesized that the firefly luciferase substrate d-luciferin and its analogs are fatty acid mimics that are ideally suited to probe the chemistry of enzymes that release fatty acid products. Here, we synthesized luciferin amides and found that these molecules are hydrolyzed to substrates for firefly luciferase by the enzyme fatty acid amide hydrolase (FAAH). In the presence of luciferase, these molecules enable highly sensitive and selective bioluminescent detection of FAAH activity in vitro, in live cells, and in vivo. The potency and tissue distribution of FAAH inhibitors can be imaged in live mice, and luciferin amides serve as exemplary reagents for greatly improved bioluminescence imaging in FAAH-expressing tissues such as the brain.

69 citations

Journal ArticleDOI
TL;DR: It is shown that mutants of firefly luciferase can discriminate between natural and synthetic substrates in the brains of live mice and that mutant luciferases that are inactive or weakly active with d-luciferin can light up brightly when treated with the aminoluciferins CycLuc1 and Cyc Luc2 or their respective FAAH-sensitive luciferin amides.
Abstract: Bioluminescence imaging is a powerful approach for visualizing specific events occurring inside live mice. Animals can be made to glow in response to the expression of a gene, the activity of an enzyme, or the growth of a tumor. But bioluminescence requires the interaction of a luciferase enzyme with a small-molecule luciferin, and its scope has been limited by the mere handful of natural combinations. Herein, we show that mutants of firefly luciferase can discriminate between natural and synthetic substrates in the brains of live mice. When using adeno-associated viral (AAV) vectors to express luciferases in the brain, we found that mutant luciferases that are inactive or weakly active with d-luciferin can light up brightly when treated with the aminoluciferins CycLuc1 and CycLuc2 or their respective FAAH-sensitive luciferin amides. Further development of selective luciferases promises to expand the power of bioluminescence and allow multiple events to be imaged in the same live animal.

47 citations

Journal ArticleDOI
TL;DR: Two-step route to a broad range of 6'-substituted luciferin analogues was developed to enable more extensive study of the 6'-functionality and revealed thioether inhibitors and unexpectedly luminogenic aryl amine derivatives.

38 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: It is demonstrated that LNPs are appropriate carriers for mRNA in vivo and have the potential to become valuable tools for delivering mRNA encoding therapeutic proteins.

554 citations

Journal ArticleDOI
23 Feb 2018-Science
TL;DR: AkaBLI produced emissions in vivo that were brighter by a factor of 100 to 1000 than conventional systems, allowing noninvasive visualization of single cells deep inside freely moving animals, and is therefore a bioengineered light source to spur unprecedented scientific, medical, and industrial applications.
Abstract: Bioluminescence is a natural light source based on luciferase catalysis of its substrate luciferin. We performed directed evolution on firefly luciferase using a red-shifted and highly deliverable luciferin analog to establish AkaBLI, an all-engineered bioluminescence in vivo imaging system. AkaBLI produced emissions in vivo that were brighter by a factor of 100 to 1000 than conventional systems, allowing noninvasive visualization of single cells deep inside freely moving animals. Single tumorigenic cells trapped in the mouse lung vasculature could be visualized. In the mouse brain, genetic labeling with neural activity sensors allowed tracking of small clusters of hippocampal neurons activated by novel environments. In a marmoset, we recorded video-rate bioluminescence from neurons in the striatum, a deep brain area, for more than 1 year. AkaBLI is therefore a bioengineered light source to spur unprecedented scientific, medical, and industrial applications.

275 citations

Journal ArticleDOI
TL;DR: The properties and applications of d-luciferin, coelenterazine, bacterial, Cypridina and dinoflagellate luciferins and their analogues along with their corresponding luciferases are described.
Abstract: Bioluminescence (BL) is a spectacular phenomenon involving light emission by live organisms. It is caused by the oxidation of a small organic molecule, luciferin, with molecular oxygen, which is catalysed by the enzyme luciferase. In nature, there are approximately 30 different BL systems, of which only 9 have been studied to various degrees in terms of their reaction mechanisms. A vast range of in vitro and in vivo analytical techniques have been developed based on BL, including tests for different analytes, immunoassays, gene expression assays, drug screening, bioimaging of live organisms, cancer studies, the investigation of infectious diseases and environmental monitoring. This review aims to cover the major existing applications for bioluminescence in the context of the diversity of luciferases and their substrates, luciferins. Particularly, the properties and applications of D-luciferin, coelenterazine, bacterial, Cypridina and dinoflagellate luciferins and their analogues along with their corresponding luciferases are described. Finally, four other rarely studied bioluminescent systems (those of limpet Latia, earthworms Diplocardia and Fridericia and higher fungi), which are promising for future use, are also discussed.

216 citations

Journal ArticleDOI
TL;DR: In vivo bioluminescence imaging is an optical molecular imaging technique used to visualize molecular and cellular processes in health and diseases and to follow the fate of cells with high sensitivity using luciferase-based gene reporters.

204 citations